Rapid Amplification of Cerebrospinal Fluid Pressure as a Possible Mechanism for Optic Nerve Sheath Bleeding in Infants With Nonaccidental Head Injury.

Purpose: Subdural hemorrhage along the optic nerve (ON) is a histopathological indicator of abusive head trauma (AHT) in infants. We sought to determine if this bleeding could be caused by an abrupt increase in intracranial pressure transmitted to cerebrospinal fluid (CSF) at the optic foramen (OF). Methods: A theoretical model is developed to simulate the effect of a pressure perturbation of maximal amplitude P applied at the optic foramen for a short duration T on the CSF-filled ON subarachnoid space (ONSAS). The ONSAS is modelled as a fluid-filled channel with an elastic wall representing the flexible ONSAS-arachnoid/dura interface. A constitutive law describing the relationship between CSF pressure and ONSAS deformation is inferred from published measurements. CSF pressure profiles along the ONSAS are examined systematically over a broad range of P and T. Results: The pressure perturbation initiated at the OF produces a pressure wave that stretches the ONSAS. This wave propagates rapidly along the ONSAS toward the scleral end of the ON, where it is reflected back toward the brain. For sufficiently small T a shock wave with amplification up to six times larger than P over a timescale of tens of milliseconds is observed at the scleral end of the ON. Comparatively smaller amplifications are observed for slower perturbations. Conclusions: A sudden increase in CSF pressure in the cranial cavity can cause a rapid expansion of the ONSAS, which may lead to rupture of the bridging blood vessels. Our study predicts a plausible mechanism for subdural hemorrhage that occurs in abusive head trauma in infants.

Assessment of neurofluid dynamics in relation to clinical improvement after tap-test: pilot study.

PURPOSE: Idiopathic Normal pressure hydrocephalus (iNPH) is an under-diagnosed in elderly patients but none of the diagnostic tests are currently sufficiently sensitive or specific. The objective of this study was to analyze the dynamics of neurofluids by PC-MRI in relation to clinical evolution as measured using the iNPH grading scale after tap-test. METHOD: We prospectively included patients with suspected iNPH. All these patients underwent PCMRI to assess craniospinal hemohydrodynamics with analysis of the stroke volume of the cephalospinal fluid (CSF) within the Sylvius' aqueduct, within the high cervical subarachnoid spaces and the arteriovenous stroke volume. By this means, we calculated a compliance index. Morphological analysis was carried out using the DESH score. The infusion test was measuring the resistance to CSF flow. We analysed all these parameters according to the clinical improvement of the patients. RESULTS: 23 patients were included. Compliance index assessed by PC-MRI was significantly higher in the group of patients with improvement > 10% (p = 0.015). CONCLUSIONS: Our study highlights the importance of investigating arteriovenous and CSF interactions in iNPH. This involves understanding the physiological and pathophysiological mechanisms related to the circulation of neurofluids. The analysis of the interactions of these neurofluids allows for a comprehensive understanding of the system.

Response to Commentary on "Structural characterization of SLYM - a 4th meningeal membrane" by Julie Siegenthaler and Christer Betsholtz.

Histological studies have for decades documented that each of the classical meningeal membranes contains multiple fibroblast layers with distinct cellular morphology. Particularly, the sublayers of the arachnoid membranes have received attention due to their anatomical complexity. Early studies found that tracers injected into the cerebrospinal fluid (CSF) do not distribute freely but are restricted by the innermost sublayer of the arachnoid membrane. The existence of restrictions on CSF movement and the subdivision of the subarachnoid space into several distinct compartments have recently been confirmed by in vivo 2-photon studies of rodents, as well as macroscopic imaging of pigs and magnetic resonance imaging of human brain. Based on in vivo imaging and immunophenotyping characterization, we identified the structural basis for this compartmentalization of the subarachnoid space, which we term 'Subarachnoid lymphatic-like membrane', SLYM. The SLYM layer engages the subarachnoid vasculature as it approaches the brain parenchyma, demarcating a roof over pial perivascular spaces. Functionally, the separation of pial periarterial and perivenous spaces in the larger subarachnoid space is critical for the maintenance of unidirectional glymphatic clearance. In light of its close apposition to the pial surface and to the brain perivascular fluid exit points, the SLYM also provides a primary locus for immune surveillance of the brain. Yet, the introduction of SLYM, in terms of its anatomic distinction and hence functional specialization, has met resistance. Its critics assert that SLYM has been described in the literature by other terms, including the inner arachnoid membrane, the interlaminate membrane, the outer pial layer, the intermediate lamella, the pial membrane, the reticular layer of the arachnoid membrane or, more recently, BFB2-3. We argue that our conception of SLYM as an anatomically and functionally distinct construct is both necessary and warranted since its functional roles are wholly distinct from those of the overlying arachnoid barrier layer. Our terminology also lends clarity to a complex anatomy that has hitherto been ill-described. In that regard, we also note the lack of specificity of DPP4, which has recently been introduced as a 'selected defining marker' of the arachnoid barrier layer. We note that DPP4 labels fibroblasts in all meningeal membranes as well as in the trabecula arachnoides and the vascular adventitial layers, thus obviating its utility in meningeal characterization. Instead, we report a set of glymphatic-associated proteins that serve to accurately specify SLYM and distinguish it from its adjacent yet functionally distinct membranes.

Different Glymphatic Kinetics in Spontaneous Intracranial Hypotension.

BACKGROUND AND PURPOSE: The glymphatic (glia-lymphatic) system is a paravascular pathway for the clearance of waste metabolites including amyloid ß from the brain. Serial T1 relaxation time measurements after the intrathecal injection of gadolinium-based contrast agents facilitate the analysis of the temporal dynamics that may be different in patients with spontaneous intracranial hypotension (SIH) and those without SIH. MATERIALS AND METHODS: 3D T1-weighted magnetization-prepared 2 rapid gradient echo sequences were acquired in 4 patients with SIH with proved CSF leaks and 12 patients without SIH before, 2-4, 6-8, and 24-48 hours after intrathecal gadobutrol injection. MR scans were warped to the Montreal Neurological Institute space and serial scans were coregistered. T1 relaxation times were measured in predefined ROIs including the subarachnoid space, cortex, white matter, and cervical lymph nodes. RESULTS: In the subarachnoid space and cortex, T1 relaxation times decreased after 2-4 and 6-8 hours before they increased again. In contrast, in the white matter of the temporal lobe T1 relaxation time still decreased after 24-48 hours. There was a striking difference in patients with SIH who did not show a clear contrast distribution within the brain parenchyma. CONCLUSIONS: T1 relaxation time curves are compatible with a convective flow driven by arterial pulsations via paravascular spaces surrounding penetrating arteries into the brain's interstitial fluid in the deep white matter. Different curves in patients with SIH and those without SIH indicate that the CSF pressure also impacts the temporal kinetics of the glymphatic system.

Morphometric Study of the Intracranial Fluid Spaces in Schizophrenia.

BACKGROUND: The intracranial fluid spaces (IFS), also known as "the extra-axial spaces," consist of the superficial cerebral sulci, the Sylvian fissures, the basal cisterns, the third ventricle, the fourth ventricle, and the two lateral ventricles. In diseases such as schizophrenia, Alzheimer's, Parkinson's, and especially hydrocephalus, IFS' enlargements are observed. OBJECTIVE: Our study aimed to determine the mean values of IFS measurements in patients with schizophrenia and compare them with healthy controls. MATERIAL AND METHODS: This work has been carried out on 188 cases, out of which 88 schizophrenia patients (56 men and 32 women) met the diagnostic criteria according to DSM-5 for schizophrenia and 100 healthy controls (50 men and 50 women). The 10 parameters have been used to evaluate IFS on magnetic resonance imaging (MRI) scans. RESULTS: The parameters showing statistically significant differences were higher in favor of the individual with schizophrenia. Except for the bifrontal index and Evan's index, most parameters (the bicaudate index, the fourth ventricle width, the fourth ventricle index, the maximum width of the anterior interhemispheric fissure, the maximum width of the right frontal subarachnoid space, the maximum width of the left frontal subarachnoid space, the maximum width of the right Sylvian fissure, and the maximum width of the left Sylvian fissure) were obtained statistically highly significant differences between the examined and control groups. CONCLUSIONS: In schizophrenia, it is more practical to evaluate brain atrophy using some parameters, especially the width of the Sylvian fissure and the bicaudate index.

Clearance of erythrocytes from the subarachnoid space through cribriform plate lymphatics in female mice.

BACKGROUND: Atraumatic subarachnoid haemorrhage (SAH) is associated with high morbidity and mortality. Proposed mechanisms for red blood cell (RBC) clearance from the subarachnoid space (SAS) are erythrolysis, erythrophagocytosis or through efflux along cerebrospinal fluid (CSF) drainage routes. We aimed to elucidate the mechanisms of RBC clearance from the SAS to identify targetable efflux pathways. METHODS: Autologous fluorescently-labelled RBCs along with PEGylated 40 kDa near-infrared tracer (P40D800) were infused via the cisterna magna (i.c.m.) in female reporter mice for lymphatics or for resident phagocytes. Drainage pathways for RBCs to extracranial lymphatics were evaluated by in vivo and in situ near-infrared imaging and by immunofluorescent staining on decalcified cranial tissue or dural whole-mounts. FINDINGS: RBCs drained to the deep cervical lymph nodes 15 min post i.c.m. infusion, showing similar dynamics as P40D800 tracer. Postmortem in situ imaging and histology showed perineural accumulations of RBCs around the optic and olfactory nerves. Numerous RBCs cleared through the lymphatics of the cribriform plate, whilst histology showed no relevant fast RBC clearance through dorsal dural lymphatics or by tissue-resident macrophage-mediated phagocytosis. INTERPRETATION: This study provides evidence for rapid RBC drainage through the cribriform plate lymphatic vessels, whilst neither fast RBC clearance through dorsal dural lymphatics nor through spinal CSF efflux or phagocytosis was observed. Similar dynamics of P40D800 and RBCs imply open pathways for clearance that do not impose a barrier for RBCs. This finding suggests further evaluation of the cribriform plate lymphatic function and potential pharmacological targeting in models of SAH. FUNDING: Swiss National Science Foundation (310030_189226), SwissHeart (FF191155).

Cerebro-spinal flow pattern in the cervical subarachnoid space of healthy volunteers: Influence of the spinal cord morphology.

INTRODUCTION: Toward further cerebro-spinal flow quantification in clinical practice, this study aims at assessing the variations in the cerebro spinal fluid flow pattern associated with change in the morphology of the subarachnoid space of the cervical canal of healthy humans by developing a computational fluid dynamics model. METHODS: 3D T2-space MRI sequence images of the cervical spine were used to segment 11 cervical subarachnoid space. Model validation (time-step, mesh size, size and number of boundary layers, influences of parted inflow and inflow continuous velocity) was performed a 40-year-old patient-specific model. Simulations were performed using computational fluid dynamics approach simulating transient flow (Sparlart-Almaras turbulence model) with a mesh size of 0.6, 6 boundary layers of 0.05 mm, a time step of 20 ms simulated on 15 cycles. Distributions of components velocity and WSS were respectively analyzed within the subarachnoid space (intervertebral et intravertebral levels) and on dura and pia maters. RESULTS: Mean values cerebro spinal fluid velocity in specific local slices of the canal range between 0.07 and 0.17 m.s-1 and 0.1 and 0.3 m.s-1 for maximum values. Maximum wall shear stress values vary between 0.1 and 0.5 Pa with higher value at the middle of the cervical spine on pia mater and at the lower part of the cervical spine on dura mater. Intra and inter-individual variations of the wall shear stress were highlighted significant correlation gwith compression ratio (r = 0.76), occupation ratio and cross section area of the spinal cord. CONCLUSION: The inter-individual variability in term of subarachnoid canal morphology and spinal cord position influence the cerebro-spinal flow pattern, highlighting the significance of canal morphology investigation before surgery.

Suprapiamadre: Análisis Etimológico y Propuesta Terminológica para la Cuarta Meninge en Terminologia Anatomica, Terminologia Neuroanatomica y Terminologia Histologica / Suprapiamadre: Etymological Analysis and Terminological Proposal for the Fourth Meninge in Terminologia Anatomica, Terminologia Neuroanatomica and Terminologia Histologica

A lo largo de la historia, el conocimiento sobre las meninges ha evolucionado desde los primeros registros en el papiro de Edwin Smith hasta la actualidad, donde se ha descrito SLYM, una cuarta meninge que separa el espacio subaracnoideo en un compartimiento superficial y otro profundo, a la que se le atribuyen funciones de barrera semipermeable y de nicho de células inmunes para la vigilancia y protección del sistema nerviosos central. La FIPAT contiene un grupo de terminologías que son mundialmente aceptadas para la descripción de las estructuras del cuerpo humano, sin embargo, en Terminologia Anatomica, Ter- minologia Neuroanatomica y Terminologia Histologica, aún no se encuentra incluido el término SLYM para representar una cuarta meninge, quizás porque sea un reciente descubrimiento. El objetivo de este estudio fue sugerir un nuevo término que concuerde con los lineamientos de la FIPAT y con las reglas de Terminología Anatómica Regular (RAT) en reemplazo de SLYM, además de proponer su inclusión en Terminologia Anatomica, Terminologia Neuroanatomica y Terminologia Histologica, previa revisión y aprobación por parte del comité respectivo de la FIPAT. Se revisó el acrónimo SLYM y los elementos que lo conforman (membrana subaracnoidea de tipo linfática), desde un enfoque etimológico, este análisis estuvo acompañado de una revisión a las reglas RAT aceptadas por la FIPAT, que fueron consideradas para examinar su cumplimiento por parte del acrónimo SLYM. Se encontró que SLYM, al igual que los términos que lo componen no cumplen totalmente con las reglas RAT. El acrónimo SLYM no proporciona una descripción adecuada de la estructura que representa, lo que contradice las reglas RAT. Se propone el término Suprapiamater como alternativa, para su inclusión en Terminologia Anatomica, Terminologia Neuroanatomica y Terminologia Histologica, basado en elementos latinos que describen su ubicación y función, mejorando la precisión y claridad en la comunicación científica.

SUMMARY: Throughout history, knowledge about the meninges has evolved from the first records in the Edwin Smith papyrus to the present, where SLYM, a fourth meninge that separates the subarachnoid space into a superficial compartment and another, has been described deep, to which semipermeable barrier and immune cell niche functions are attributed for the surveillance and protection of the central nervous system. The FIPAT contains a group of terminologies that are globally accepted for the description of the structures of the human body, however, in Terminologia Anatomica, Terminologia Neuroanatomica and Terminologia Histologica, the term SLYM to represent a fourth meninge is not yet included, perhaps because be a recent discovery. The objective of this study was to suggest a new term that agrees with the FIPAT guidelines and with the Regular Anatomical Terminology (RAT) rules to replace SLYM, in addition to proposing its inclusion in Terminologia Anatomica, Terminologia Neuroanatomica and Terminologia Histologica, previously review and approval by the respective FIPAT committee. The acronym SLYM and the elements that make it up (Subarachnoid Lymphatic-like Membrane) were reviewed from an etymological approach. This analysis was accompanied by a review of the RAT rules accepted by FIPAT, which were considered to examine their compliance by the acronym SLYM. It was found that SLYM, like the terms that compose it, do not fully comply with the RAT rules. The SLYM acronym does not provide an adequate description of the structure it represents, which contradicts the RAT rules. The term suprapiamater is proposed as an alternative, for inclusion in Terminologia Anatomica, Terminologia Neuroanatomica and Terminologia Histologica, based on Latin elements that describe its location and function, improving precision and clarity in scientific communication.

Perivascular spaces around arteries exceed perivenous spaces in the mouse brain.

The perivascular space (PVS) surrounds cerebral blood vessels and plays an important role in clearing waste products from the brain. Their anatomy and function have been described for arteries, but PVS around veins remain poorly characterized. Using in vivo 2-photon imaging in mice, we determined the size of the PVS around arteries and veins, and their connection with the subarachnoid space. After infusion of 70 kD FITC-dextran into the cerebrospinal fluid via the cisterna magna, labeled PVS were evident around arteries, but veins showed less frequent labeling of the PVS. The size of the PVS correlated with blood vessel size for both pial arteries and veins, but not for penetrating vessels. The PVS around pial arteries and veins was separated from the subarachnoid space by a thin meningeal layer, which did not form a barrier for the tracer. In vivo, FITC-dextran signal was observed adjacent to the vessel wall, but minimally within the wall itself. Post-mortem, there was a significant shift in the tracer's location within the arterial wall, extending into the smooth muscle layer. Taken together, these findings suggest that the PVS around veins has a limited role in the exchange of solutes between CSF and brain parenchyma.

Evaluating the effect of injection protocols on intrathecal solute dispersion in non-human primates: an in vitro study using a cynomolgus cerebrospinal fluid system.

BACKGROUND: Achieving effective drug delivery to the central nervous system (CNS) remains a challenge for treating neurological disorders. Intrathecal (IT) delivery, which involves direct injection into the cerebrospinal fluid (CSF), presents a promising strategy. Large animal studies are important to assess the safety and efficacy of most drugs and treatments and translate the data to humans. An understanding of the influence of IT injection parameters on solute distribution within the CNS is essential to optimize preclinical research, which would potentially help design human clinical studies. METHODS: A three-dimensional (3D) in vitro model of a cynomolgus monkey, based on MRI data, was developed to evaluate the impact of lumbar injection parameters on intrathecal solute dispersion. The parameters evaluated were (a) injection location, (b) bolus volume, (c) flush volume, (d) bolus rate, and (e) flush rate. To simulate the CSF flow within the subarachnoid space (SAS), an idealized CSF flow waveform with both cardiac and respiratory-induced components was input into the model. A solution of fluorescein drug surrogate tracer was administered in the lumbar region of the 3D in vitro model filled with deionized water. After injection of the tracer, the CSF system wide-solute dispersion was imaged using high-resolution cameras every thirty seconds for a duration of three hours. To ensure repeatability each injection protocol was repeated three times. For each protocol, the average spatial-temporal distribution over three hours post-injection, the area under the curve (AUC), and the percent injected dose (%ID) to extra-axial CSF (eaCSF) at three hours were determined. RESULTS: The changes to the lumbar injection parameters led to variations in solute distribution along the neuro-axis. Specifically, injection location showed the most impact, enhancing the delivery to the eaCSF up to + 10.5%ID (p = 0.0282) at three hours post-injection. Adding a post-injection flush of 1.5 ml at 1 ml/min increased the solute delivery to the eaCSF by + 6.5%ID (p = 0.0218), while the larger bolus volume resulted in a + 2.3%ID (p = 0.1910) increase. The bolus and flush rates analyzed had minimal, statistically non-significant effects. CONCLUSION: These results predict the effects of lumbar injection parameters on solute distribution in the intrathecal space in NHPs. Specifically, the choice of injection location, flush, and bolus volume significantly improved solute delivery to eaCSF. The in vitro NHP CSF model and results offer a system to help predict and optimize IT delivery protocols for pre-clinical NHP studies.

Radio-pathologic correlation: no pial angioma-subarachnoid varicose network drainage pathway in Sturge-Weber syndrome.

PURPOSE: The traditional imaging findings reported in Sturge-Weber syndrome (SWS) include endpoints of cortical injury-cortical atrophy and cortical calcifications-but also what has been termed a "leptomeningeal angiomatosis," the latter recognized and reported as a leptomeningeal enhancement on magnetic resonance imaging (MRI). The objective of this study is to demonstrate through neuropathological correlation that the "leptomeningeal angiomatosis" in patients with Sturge-Weber syndrome (SWS), represents a re-opened primitive venous network in the subarachnoid space that likely acts as an alternative venous drainage pathway, seen separately to abnormal pial enhancement. MATERIALS AND METHODS: Retrospective review of MR imaging and surgical pathology of patients that underwent surgery for epilepsy at a tertiary, children's hospital. A pediatric radiologist with more than 20 years of experience reviewed the MR imaging. Surgically resected brain specimens that had been sectioned and fixed in 10% paraformaldehyde for histologic processing, following processing and paraffin embedding, were cut into 5-µm unstained slides which were subsequently stained with hematoxylin and eosin (H&E). Slides were re-examined by a board-certified pediatric neuropathologist, and histologic features specifically relating to cerebral surface and vascularity were documented for correlation with MR imaging of the resected region performed prior to resection. RESULTS: Five patients were reviewed (3 boys and 2 girls; the median age at the onset of seizures was 12 months (IQR, 7 to 45 months); the median age at surgery was 33 months (IQR, 23.5 to 56.5 months)). Surgical procedures included the following: 4, hemispherotomy (right: 2, left: 2) and 1, hemispherectomy (right). A subarachnoid space varicose network was present on both MRI and histology in 4 patients. Calcifications were seen on both MRI and histology in 3 patients. Abnormal leptomeningeal enhancement was present in 5 patients and seen separately from the subarachnoid vascular network in 4 patients. CONCLUSION: Histopathology confirmed the MRI findings of a subarachnoid space varicose network seen separately from leptomeningeal enhancement and presumed to represent an alternative venous drainage pathway to compensate for maldevelopment of cortical veins, the primary abnormality in SWS. No pial-based angioma was identified.

Collapse or distention of the perioptic space in children - What does it mean to pediatric radiologists? Comprehensive review of perioptic space evaluation.

The perioptic space comprises the subarachnoid space [SAS] of the optic nerve communicating with the SAS of the central nervous system. Pressure variations in the SAS of the central nervous system can be transmitted to the optic papilla through the perioptic space. Variations in the diameter of the perioptic space serve as an important indicator for select intracranial pathologies in the pediatric population. Though the perioptic space can be evaluated using various imaging modalities, MRI is considered highly effective due to its superior soft tissue resolution. With advancement in MR imaging techniques, high-resolution images of the orbits can provide improved visualization of the perioptic space. It is imperative for the pediatric radiologist to routinely assess the perioptic space on brain and orbit MR imaging, as it can prompt exploration for additional features associated with select intracranial pathologies, thus improving diagnostic accuracy. This article reviews basic anatomy of the perioptic space, current understanding of the CSF dynamics between the perioptic space and central nervous system SAS, various imaging modalities utilized in the assessment of the perioptic space, MRI sequences and the optimal parameters of specific sequences, normal appearance of the perioptic space on MR imaging, and various common pediatric pathologies which cause alteration in the perioptic space.

Comparison of subarachnoid administration of low-dose bupivacaine and lidocaine in healthy goats.

OBJECTIVE: This study aimed to compare the effects of low-dose subarachnoid injections of 2% lidocaine (LIDO) and 0.5% bupivacaine (BUPI) in goats. ANIMALS: 6 healthy, privately owned female goats. METHODS: In this randomized blind crossover clinical trial, each goat received 0.05 mL/kg-1 of LIDO, BUPI, or sterile saline solution into the lumbosacral subarachnoid space, with a seven-day washout. Cardiorespiratory variables, rectal temperature, and somatosensory (pinprick) and motor (ataxia) functions were recorded at baseline (time 0) and 2, 5, 10, 15, and 30 minutes after injection, then every 20 minutes until the goat was standing and able to walk. Time to regain somatosensory and motor functions was compared between treatments using Kaplan-Meier survival curves and the Cox proportional hazards model. Linear mixed-effects models were used to compare cardiorespiratory variables between treatments and over time. A P value ≤ .05 was considered significant. RESULTS: Somatosensory recovery was longer with BUPI, though not statistically significant. The median time to stand was 50 (50, 67) minutes after LIDO injection and 104 (101, 156) minutes after BUPI injection (P = .031). The median time to walk was 72 (54, 85) minutes after LIDO versus 225 (220, 245) minutes after BUPI injection (P = .031). Cardiovascular and respiratory variables showed no significant differences between treatments. CLINICAL RELEVANCE: Despite prolonged ataxia with BUPI, pinprick sensation recovery did not differ. At reduced doses, both LIDO and BUPI are deemed acceptable for short procedures of the flank, pelvic limb, or tail in healthy goats.

Idiopathic normal pressure hydrocephalus: Validation of the DESH score as a prognostic tool for shunt surgery response.

OBJECTIVE: Several radiological markers have been linked to clinical improvement after shunt surgery for idiopathic normal pressure hydrocephalus (iNPH). However, iNPH has no pathognomonic feature, and patients are still diagnosed as probable, possible, or unlikely cases based on clinical symptoms, imaging findings, and invasive supplementary tests. The predictive value of the disproportionately enlarged subarachnoid space hydrocephalus (DESH) score is not yet conclusively determined, but it might offer a more accurate diagnostic method. The aim of the present retrospective cohort study was to validate the predictive power of the DESH score for clinical improvement after shunt surgery in iNPH patients. METHODS: We retrospectively obtained presurgical MRI and/or CT scans from 71 patients with iNPH who underwent ventriculoperitoneal shunt surgery. Radiological images were evaluated for Evans index (EI), corpus callosal angle (CA), tight high convexity (THC), Sylvian fissure dilation, and focal sulci dilation. These markers were aggregated to determine the DESH score. Patient journal entries were used to subjectively determine the extent of improvement in gait function, urinary incontinence, and/or cognition as a measure of shunt surgery response. RESULTS: Multiple logistic regression analysis, controlling for age and sex (α = 0.05), showed that DESH score was significantly correlated (OR 1.77) with subjective shunt-surgery response at a minimum of 1-month follow-up. Patients with higher DESH scores were more likely to have a favorable response to shunt surgery. CONCLUSION: Aggregating radiological markers into the DESH score is useful for predicting shunt responders among iNPH patients and can aid the selection of patients for surgery. These findings provide further support for the DESH score as a diagnostic tool for iNPH.

Prospective measurement of the width of cerebrospinal fluid spaces by cranial ultrasound in neurologically healthy children aged 0-19 months.

BACKGROUND: Ultrasound (US) is often the first method used to look for brain or cerebrospinal fluid (CSF) space pathologies. Knowledge of normal CSF width values is essential. Most of the available US normative values were established over 20 years ago, were obtained with older equipment, and cover only part of the age spectrum that can be examined by cranial US. This prospective study aimed to determine the normative values of the widths of the subarachnoid and internal CSF spaces (craniocortical, minimal and maximal interhemispheric, interventricular, and frontal horn) for high-resolution linear US probes in neurologically healthy infants and children aged 0-19 months and assess whether subdural fluid collections can be delineated. METHODS: Two radiologists measured the width of the CSF spaces with a conventional linear probe and an ultralight hockey-stick probe in neurologically healthy children not referred for cranial or spinal US. RESULTS: This study included 359 neurologically healthy children (nboys = 178, 49.6%; ngirls = 181, 50.4%) with a median age of 46.0 days and a range of 1-599 days. We constructed prediction plots, including the 5th, 50th, and 95th percentiles, and an interactive spreadsheet to calculate normative values for individual patients. The measurements of the two probes and the left and right sides did not differ, eliminating the need for separate normative values. No subdural fluid collection was detected. CONCLUSION: Normative values for the widths of the subarachnoid space and the internal CSF spaces are useful for evaluating intracranial pathology, especially when determining whether an increase in the subarachnoid space width is abnormal.

Transcriptomic analysis of subarachnoid cysts of Taenia solium reveals mechanisms for uncontrolled proliferation and adaptations to the microenvironment.

Subarachnoid neurocysticercosis (SANCC) is caused by an abnormally transformed form of the metacestode or larval form of the tapeworm Taenia solium. In contrast to vesicular parenchymal and ventricular located cysts that contain a viable scolex and are anlage of the adult tapeworm, the subarachnoid cyst proliferates to form aberrant membranous cystic masses within the subarachnoid spaces that cause mass effects and acute and chronic arachnoiditis. How subarachnoid cyst proliferates and interacts with the human host is poorly understood, but parasite stem cells (germinative cells) likely participate. RNA-seq analysis of the subarachnoid cyst bladder wall compared to the bladder wall and scolex of the vesicular cyst revealed that the subarachnoid form exhibits activation of signaling pathways that promote proliferation and increased lipid metabolism. These adaptions allow growth in a nutrient-limited cerebral spinal fluid. In addition, we identified therapeutic drug targets that would inhibit growth of the parasite, potentially increase effectiveness of treatment, and shorten its duration.

Age related cerebrospinal fluid flow dynamics in the subarachnoid space of the optic nerve in patients with normal tension glaucoma, measured by diffusion weighted MRI.

BACKGROUND/OBJECTIVES: We aimed to measure cerebrospinal fluid (CSF) flow rates in the subarachnoid space (SAS) of the optic nerve (ON) by applying non-invasive diffusion-weighted MRI in patients with normal tension glaucoma (NTG) compared to age-matched controls. SUBJECTS/METHODS: In this prospective study, an analysis of diffusion-weighted images of 26 patients with NTG (49ONs) and age-matched volunteers (52ONs) was conducted. Subjects were classified into 4 groups: group I (50-59 y., n = 12 eyes), group II (60-69 y., n = 16 eyes), group III (70-79 y., n = 18 eyes) and group IV ( > 80 y., n = 6 eyes) for NTGs and healthy volunteers, respectively. The flow-range ratio (FRR) between the frontal lobe SAS and the SAS of the ON was calculated for each age category group and then compared between age-categories as well as between NTGs and controls. RESULTS: The mean FRR for age groups were (I) 0.54 ± 0.06 and 0.62 ± 0.03 (p < 0.05), (II) 0.56 ± 0.08 and 0.63 ± 0.03 (p < 0.05), (III) 0.54 ± 0.06 and 0.62 ± 0.02 (p < 0.001) as well as (IV) 0.61 ± 0.03 and 0.61 ± 0.04, for NTGs and controls, respectively. Using pooled data, the difference between the FRR in NTGs and controls was statistically significant (p < 0.0001). There were no statistically significant differences within the age categories of the control group. When comparing the FRR of NTGs by age categories, no statistically significant difference was found between the subgroups. CONCLUSIONS: FRR was significantly reduced in NTGs compared to age-matched controls without any significant differences within the age groups themselves. Given the physiological importance of CSF for the integrity of neurons, axons and glial cells, reduced CSF flow dynamics might be part of the underlying neurodegenerative process of NTG.

Comparison of sequential and mixture injections of opioids and hyperbaric bupivacaine for subarachnoid block for lower segment caesarean section: a randomised controlled study.

INTRODUCTION: Opioids are commonly added to local anaesthetic for subarachnoid block for caesarean section due to their synergistic effects. The physiochemical characteristics of opioids suggest premixing with hyperbaric bupivacaine may limit their distribution within the CSF. We studied the effect of a separate injection with a combination of bupivacaine, morphine and fentanyl on block characteristics, haemodynamic changes, postoperative pain and patient satisfaction. METHOD: Following ethical approval and informed consent, a prospective double-blinded randomised controlled trial was performed in a university hospital. A total of 126 patients undergoing caesarean section were randomised to two groups. In group M, the premixed group, patients received 12 mg of hyperbaric bupivacaine, 20 mcg of fentanyl and 100 mcg of morphine injected as a single mixture. In group S, the separate injection group, patients received the same drugs in separate injections. Measurements included haemodynamics, block distribution, intra- and postoperative pain, as well as patient satisfaction. RESULTS: Patients in both groups had similar block height, time to maximum sensory block, time to block regression and motor block. However, haemodynamics were different between the groups. The proportion of systolic hypotension episodes was greater in group S [159/1320 (12.05%)] than group M [113/1452 (7.78%)], with P = 0.0002. Moreover, a greater amount of ephedrine was administered in group S than group M, with values 12.09 (8.1) and 9.09 (8.5) mg respectively (P = 0.001). Additionally, postoperative pain, as measured by the Visual Analogue Scale (VAS), was greater in group M, with a VAS of 4.6 (1.7), vs. group S, which recorded a VAS of 3.8 (2.0) (P = 0.017). CONCLUSION: Sequential injection of intrathecal opioids and hyperbaric bupivacaine resulted in greater early haemodynamic instability and slightly better postoperative analgesia without any difference in block height or patient satisfaction. CLINICAL TRIAL REGISTRATION: NCT04403724.